Abstract P3-12-04: A phase 2, multi-center, open label study evaluating the efficacy and safety of GRN1005 alone or in combination with trastuzumab in patients with brain metastases from breast cancer
Notice bibliographique
Résumé
Abstract Rationale: Treatment of brain metastasis (BM) remains an unmet medical need due to the inability of most anti-cancer agents to effectively cross the blood-brain barrier (BBB). GRN1005 is a peptide-drug conjugate (PDC) consisting of 3 molecules of paclitaxel conjugated to a 19-amino acid peptide, Angiopep-2. GRN1005 effectively penetrates the BBB by targeting the low-density lipoprotein receptor-related protein 1 (LRP1), which is expressed on the surface of the BBB and on certain neoplastic cells. In a phase 1 study, GRN1005 demonstrated encouraging anti-tumor activity in breast cancer (BC) patients with BM. Methods: Up to 157 patients (pts) with measurable BM from BC, with or without extra-cranial disease, are currently being enrolled in an ongoing open label study. Prior cranial irradiation is allowed but lesions previously treated with stereotactic radiosurgery (SRS) are excluded from the efficacy analysis. All currently enrolled pts received GRN1005 at a starting dose of either 650 or 550 mg/m2 IV every three weeks, until intra-cranial disease progression (iPD), unacceptable toxicity, or initiation of non-protocol systemic therapy. HER2 positive pts received concomitant trastuzumab. The primary endpoint is intra-cranial objective response rate (iORR), as assessed by independent review using CNS RECIST 1.1. Additional endpoints include safety, duration of intra-cranial response, 3-month intra-cranial progression free survival (iPFS3), extra-cranial ORR, and neurocognitive function. Results: As of 4 June 2012, 24 pts (13 at 650 mg/m2 and 11 at 550 mg/m2) have been treated with a median of 2 cycles of GRN1005 (range 1–5). Median age was 51.5 years (34–68) and 14 (58%) pts have HER2-positive disease. Pts received a median of 6 (3–14) prior systemic regimens; 19 had received prior whole brain radiation therapy (WBRT) ± SRS and 2 had received prior SRS only (data pending on 3 pts). Six (25%) pts have discontinued treatment with GRN1005, including 2 due to iPD and 2 due to adverse events (AE). One additional pt had clinical progression and discontinued GRN1005. The AEs observed at 650 mg/m2 are qualitatively consistent with conventional paclitaxel but are more frequent and more severe than observed with q3 week paclitaxel which led to a protocol amendment and dose reduction to 550 mg/m2 for all subsequent pts. Among all treated pts, the most frequent AEs were neutropenia (75%), fatigue (50%), mucositis (33%), neuropathy (29%), and diarrhea (25%). Notable Grade 3–4 AEs were neutropenia in 12 pts (including 1 case of febrile), and arthralgia, fatigue, and rash in 3 pts each. Preliminary anti-tumor activity has been observed in both intra-cranial and extra-cranial lesions. Conclusions: GRN1005 is a promising treatment for BM associated with breast cancer and demonstrates a safety profile qualitatively similar to paclitaxel dosed every 3 weeks. Due to tolerability concerns at the 650 mg/m2 dose, the 550 mg/m2 dose is currently being evaluated in these heavily pretreated BC pts. Updated efficacy and safety data will be presented at the meeting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-04.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».